Archive for June, 2013

RSC/BMOS Young Investigator Award – Closing date 15 July 2013

15th BMOSThe RSC is delighted to announce a fantastic opportunity for Early Career Researchers to attend the 15th Brazilian Meeting on Organic Synthesis (BMOS) taking place in Campos do Jordão, Brazil, 10-13 November 2013. The conferences combines plenary and invited lectures from distinguished leaders in the field to discuss modern aspects of the art of organic synthesis. The full programme and list of speakers can be viewed via the conference website.

The Organic Division of the RSC will allocate awards to allow four outstanding researchers (two from the UK and two from Latin America) to attend the conference. Applicants must be 40 years old or under on the closing date – 15 July 2013. The winner will be selected by a selection committee which will include members of the RSC Organic Division and BMOS Organising Committee. Winners will receive a free registration, a certificate, an invitation to deliver a flash presentation and a generous contribution towards travel and accommodation. For more information and to apply visit: http://rsc.li/bmos15

Applications should be sent to RSC Science by closing date 15 July 2013  with email subject RSC/BMOS Young Investigator Award

For any queries please contact science@rsc.org

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Carboxylate-isostere analogs of daptomycin: synthesizing the next generation of antibiotics

The emergence of multi-drug resistant bacterial infections has created a pressing need for the identification of new drugs. This HOT article describes the chemical modification of daptomycin, an antibiotic used to treat Gram-positive bacterial infections.  Because of its anionic character daptomycin has a high affinity to pulmonary surfactants, but this limits its use in the treatment of pulmonary infections.

Scott Miller and co-workers hypothesized that reducing surfactant interactions may increase the antibiotic activity of daptomycin. Consequently, they set out to convert the daptomycin carboxylic acid moieties to carboxylate isosteres. This paper reports a direct and efficient procedure to produce isostere analogues of daptomycin, suppressing backbone-cyclization side reactions. The use of a high resolution UPLC-MS/MS technique to characterise the synthetic products by fragmentation analysis is also described.

carboxylate-isostere analogs of daptomycin

An efficient chemical synthesis of carboxylate-isostere analogs of daptomycin
Sabesan Yoganathan, Ning Yin, Yong He, Michael F. Mesleh, Yu Gui Gu and Scott J. Miller
DOI:
10.1039/C3OB40924D

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Latest HOT articles in OBC

Promiscuity of a modular polyketide synthase towards natural and non-natural extender units
Irina Koryakina, John B. McArthur, Matthew M. Draelos and Gavin J. Williams
DOI: 10.1039/c3ob40633d

Promiscuity of a modular polyketide synthase towards natural and non-natural extender units

Synthesis of bis-α,α′-amino acids through diastereoselective bis-alkylations of chiral Ni(II)-complexes of glycine
Jiang Wang, Hong Liu, José Luis Aceña, Daniel Houck, Ryosuke Takeda, Hiroki Moriwaki, Tatsunori Sato and Vadim A. Soloshonok
DOI: 10.1039/c3ob40594j

Synthesis of bis-α,α′-amino acids through diastereoselective bis-alkylations of chiral Ni(II)-complexes of glycine

Aerobic C–H amination of tetrahydrocarbazole derivatives via photochemically generated hydroperoxides
Naeem Gulzar and Martin Klussmann
DOI: 10.1039/c3ob40919h

Nanomolar cholera toxin inhibitors based on symmetrical pentavalent ganglioside GM1os-sym corannulenes
Martin Mattarella, Jaime Garcia-Hartjes, Tom Wennekes, Han Zuilhof and Jay S. Siegel
DOI: 10.1039/c3ob40438b

Nanomolar cholera toxin inhibitors based on symmetrical pentavalent ganglioside GM1os-sym corannulenes

Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocides
Drew Bowie, Paria Parvizi, Dustin Duncan, Christopher J. Nelson and Thomas M. Fyles
DOI: 10.1039/c3ob40593a

Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocides

All free to access for 4 weeks!

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Meet the team at ESOC 2013

 I will shortly be attending the 18th European Symposium on Organic Chemistry (ESOC 2013) held in Marseilles, France, 7-12 July, and if you too are in attendance, I’d love to meet you there!

Dr Marie Cote, Oganic & Biomolecular Chemistry Deputy Editor

Please let us know if you will also be in attendance and would like to arrange a meeting – simply email us at the OBC editorial office.

OBC is delighted to be a media partner of the conference, and there’s lots to look forward to again on this 18th edition of the symposium:

  • Prof. Ben Feringa (University of Groningen, The Netherlands) will be presented with the 2013 Lilly European Distinguished Award,
  • Prof. Nazario Martin (Universidad Complutense de Madrid, Spain) is the recipient of the 2012 EuCheMs Lecture Award, and
  • Dr Joel Turconi (Sanofi, France) will present the SANOFI Lecture

Plenary lectures at the symposium will be given by :

  • Prof. Alexandre Alexakis (University of Geneva, Swiss)
  • Prof. Fernando P. Cossio (University of the Basque Country, Spain)
  • Prof. Ben Davis (University of Oxford, UK)
  • Prof. Frank Glorius (University of Muenster, Germany)
  • Prof. David MacMillan (Princeton University, USA)
  • Prof. Eiichi Nakamura (University of Tokyo, Japan)
  • Prof. Michael Orfanopoulos (University of Crete, Greece)
  • Prof. Joost Reek (Van ‘t Hoff Institute for Molecular Sciences, The Netherlands)
  • Prof. Raffaele Riccio (Universita degli studi di Salerno, Italy)
  • Prof. Doug Stephan (University of Toronto, Canada)

Access the full scientific programme

    I look forward to meeting many of you in Marseilles!

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Stirring microwave synthesis

It is next to impossible to achieve good mixing with traditional magnetic stir bars in the cylindrical vessels used in microwave synthesis. So scientists in Austria have designed a new stir bar. 

Stirring-up-microwave-synthesis_c3ob40790j_300mMicrowave synthesis is becoming more popular thanks to the dramatically reduced reactions times and improved yields it offers. However, as the majority of these reactions involve a small narrow reaction vessel, traditional horizontal stir bars often result in inefficient mixing which can cause temperature gradients to develop and reduce product yields. 

Magnetic stirring usually involves a polymer coated AlNiCo or ferrite magnet and relies on the establishment of a liquid flow induced by centrifugal forces. These flow patterns involve a downward liquid motion towards the centre and an upward motion at the vessel wall. However, the strength of the magnet decreases rapidly over a period of months when subjected to the high temperatures of microwave synthesis and the limited size of the vessel restricts the establishment of flow patterns. 

‘We noticed that in some instances the agitation of the reaction mixture using a standard magnetic stir bar was very poor. Sometimes the stirrer was not moving at all,’ says Oliver Kappe whose team at the University of Graz used a camera to look at a microwave system before designing the new stir bar. 

Choice of magnetic material and shape were thought to be key to the success of the new stir bar. Vertical blade extensions were added to a more robust Sm2Co17 rare earth magnet. This not only extends the life of the stir bar but also significantly enlarges the cross-sectional area of the stirrer. A gap in the centre of the bar guarantees backflow which enforces flow patterns and extended blades mean that even the upper part of the system receives efficient mixing with the incorporation of additional holes and cut-outs inducing additional turbulence.

Read the full story in Chemistry World 

Design and evaluation of improved magnetic stir bars for single-mode microwave reactor
David Obermayer, Markus Damm and C. Oliver Kappe
Org. Biomol. Chem., 2013, Accepted Manuscript
DOI: 10.1039/C3OB40790J

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Switching chirality in amino acids

An international team of scientists has developed a purely chemical approach to interconvert L- and D-amino acids. This method could rival enzymatic routes used in industry, and enable cheaper production of some pharmaceuticals. interconversion-of-amino-acids_c3ob40541a_300m

 While L-amino acids are an inexpensive and renewable source of chiral molecules, used by all cells to synthesise proteins, D-amino acids are scarce in nature and consequently more expensive. Despite their rarity in biological systems, D-amino acids are widely used in the pharmaceutical industry, occurring in many drugs, including antibiotics such as penicillin and anticancer agents such as goserelin.

Currently, D-amino acids are prepared industrially by enzymatically resolving racemic mixtures of amino acids. A readily available source of D-amino acids would obviate the need for resolution, simplifying synthetic routes to many pharmaceuticals.

Vadim Soloshonok, Ikerbasque Research Professor at the University of the Basque Country, Spain, and his colleagues, used inexpensive nickel(II) acetate and a modularly designed chiral ligand derived from α-(phenyl)ethylamine to transform natural amino acids into their unnatural enantiomers. A Ni(II) amino acid Schiff base complex with three stereogenic centres, including a stereogenic nitrogen, was formed under mild and operationally simple reaction conditions. The complex enables the stereocontrolled deprotonation of the α-carbon of amino acids to invert their stereochemistry.

Soloshonok says that this methodology could have a potentially huge impact on the multi-billion dollar amino acid market. ‘D-amino acids are starting materials in the synthesis of pharmaceutical drugs and if we can reduce the price of the starting materials we can make the pharmaceuticals more affordable to people.’

Read the full story in Chemistry World

Chemical approach for interconversion of (S)- and (R)-α-amino acids
Alexander E. Sorochinsky, Hisanori Ueki, José Luis Aceña, Trevor K. Ellis, Hiroki Moriwaki, Tatsunori Sato and Vadim A. Soloshonok
DOI: 10.1039/c3ob40541a

Free to access for 4 weeks

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An end to chasing molecules that were never there?

Imagine finally completing a 30 step total synthesis only to discover that the molecule you were aiming for was the wrong one. The consequences of structural misassignment of complex organic molecules can be costly and time consuming, not to mention frustrating. Now, a new NMR method aims to highlight errors in proposed structures at a much earlier stage, preventing such scenarios.

NMR spectroscopy is a standard tool for elucidating the structure of organic molecules. This may be a straightforward job when confirming the identity of small molecules. However, in the case of complex molecules, the task becomes much more difficult and errors can result in the wrong structure being proposed.

Ariel Sarotti from the Rosario National University, Argentina, has developed a new, computationally inexpensive method combining calculated and experimental 13C NMR data to flag up incorrect structures. This rapid and simple process can determine if a candidate structure is incorrect, using trained artificial neural networks (ANNs) to find patterns in both the calculated and experimental data to do the decision making. A set of 200 molecules with known correct and incorrect NMR assignments was used to create and train the system. The subsequent testing phase correctly identified the incorrect structures of a set of 26 natural products. While some knowledge of computational chemistry is required, Sarotti’s development of an Excel spreadsheet tool will allow chemists to use the method without being experts in ANNs, making it much more accessible.

new-NMR-method_c3ob40843d-ga_630

Read the full story in Chemistry World

Successful combination of computationally inexpensive GIAO 13C NMR calculations and artificial neural network pattern recognition: a new strategy for simple and rapid detection of structural misassignments
DOI: 10.1039/C3OB40843D

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New neuraminidase inhibitors to combat bird flu

Avian influenza is an RNA virus, with subtypes classified by hemagglutanin and neuraminidase (NA) viral surface membrane glycoproteins. There are 9 NA serotypes of influenza A circulating within the avian population (N1-N9). At present, there are two commercially available NA inhibitors, oseltamivir (Tamiflu) and zanamivir (Relenza) and the threat of drug-resistant viruses is driving the development of new NA inhibitors.

The X-ray crystal structure of zanamivir-bound N1 show the C-4 guanidino group of zanamivir  located near the 150-loop adjacent to the active site of NA.  In this HOT article, Tsu-An Hsu, Chun-Cheng Lin and co-workers report the synthesis and inhibitory activity of a series of zanamivir derivatives with modified C-4 guanidino groups. The new, structurally modified zanamivir analogues retained inhibitory activity against H1N1 and H3N3 avian influenza viruses.

Synthesis of acylguanidine zanamivir derivatives as neuraminidase inhibitors and the evaluation of their bio-activities

Synthesis of acylguanidine zanamivir derivatives as neuraminidase inhibitors and the evaluation of their bio-activities
Chien-Hung Lin, Tsung-Che Chang, Anindya Das, Ming-Yu Fang, Hui-Chen Hung, Kai-Cheng Hsu, Jinn-Moon Yang, Mark von Itzstein, Kwok Kong T. Mong, Tsu-An Hsu and Chun-Cheng Lin
DOI: 10.1039/c3ob40624e

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